Adrenal hypoplasia is a rare, life-threatening congenital disorder. Here we define a new form of syndromic adrenal hypoplasia, which we propose to term MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome. By exome sequencing and follow-up studies, we identified 11 patients with adrenal hypoplasia and common extra-adrenal features harboring mutations in SAMD9. Expression of the wild-type SAMD9 protein, a facilitator of endosome fusion, caused mild growth restriction in cultured cells, whereas expression of mutants caused profound growth inhibition. Patient-derived fibroblasts had restricted growth, decreased plasma membrane EGFR expression, increased size of early endosomes, and intracellular accumulation of giant vesicles carrying a late endosome marker. Of interest, two patients developed myelodysplasitc syndrome (MDS) that was accompanied by loss of the chromosome 7 carrying the SAMD9 mutation. Considering the potent growth-restricting activity of the SAMD9 mutants, the loss of chromosome 7 presumably occurred as an adaptation to the growth-restricting condition.

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Urinary tract infection (UTI) in children requires early diagnosis and treatment to prevent repeated UTI and renal scarring. This study aimed to evaluate the usefulness of the point-of-care Gram stain by physicians for suspected UTI in children at Okinawa Chubu Hospital as a rapid diagnostic test. A single-center, retrospective study was undertaken between January 2011 and December 2015. Patients aged 36 months or younger who were reviewed had suspected UTI in the emergency room or outpatient clinic. Urine culture, urinalysis, and point-of-care Gram stain were performed on a single specimen. Patients with structural or functional urological defects requiring routine catheterization were excluded. We compared the diagnostic performance among the rapid diagnostic tests (i.e., pyuria, point-of-care Gram stain, or both). Kappa statistics were used to evaluate the agreement between the results of point-of-care Gram stain and morphotypes of urine culture with the 95% CI (bias corrected bootstrap interval). We also analyzed which antibiotics were more susceptible to the bacteria of urine culture results, selected by the results of point-of-care Gram stain or empirical treatment based on the Japanese guidelines by McNemar test. Of 1594 patients reviewed in the study, 1546 were eligible according to our inclusion criteria. Using urine culture as the gold standard for UTI, the sensitivity and specificity of pyuria were 73.2% and 95.1%, whereas those of the point-of-care Gram stain were 81.4% and 98.2%, respectively. The concordance rate between the morphotypes of bacteria detected by point-of-care Gram stain and those of urine culture was 0.784 (kappa coefficient) (95% CI 0.736–0.831). Furthermore, the proportion of “susceptible” in the minimum inhibitory concentration of pathogen-targeted treatment based on the point-of-care Gram stain was higher than that of empirical therapy (exact McNemar significance probability: .0001). Our analysis suggests that the point-of-care Gram stain is a useful rapid diagnostic tool for suspected UTI in young children. Pathogen-targeted treatment based on the point-of-care Gram stain would lead to better antibiotic selection compared with empirical therapy.

Vitamin D deficiency rickets remains a common condition that is best managed by education and disease prevention.

Abstract. Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of adrenal insufficiency, achalasia and alacrima. This syndrome, also known as triple A syndrome, is now known to be caused by mutations in the AAAS gene. In the present study, we report two new patients of Allgrove syndrome with mutations in the AAAS gene. Patient 1 was a 22-year-old Japanese woman, born to consanguineous parents. She was confirmed to have adrenal insufficiency at the age of 3 years and 6 months. She developed alacrima and bilateral optic nerve atrophy at the age of 8 years. She had been noticed to have dysphagia. Based on these findings, she was diagnosed as having Allgrove syndrome. Mutation analysis revealed a novel homozygous point mutation in exon 7 of her AAAS gene, changing codon 194 encoding Arg (CGA) to a stop codon (TGA) (R194X). Patient 2 was a 7-year-old Japanese boy, born to consanguineous parents. At the age of 1 year, he was noticed to be unable to produce tears. He was confirmed to have adrenal insufficiency, mental retardation and spastic diplegia at the age of 5 years and 4 months. He was tentatively diagnosed as having Allgrove syndrome, although he has never complained of dysphasia. Mutation analysis revealed a homozygous point mutation in exon 4 of his AAAS gene, changing codon 119 encoding Arg (CGA) to a stop codon (TGA) (R119X). Both of the R119X and R194X mutations are predicted to result in truncated and non-functioning ALADIN proteins, and thus the diagnosis of Allgrove syndrome was confirmed by the mutation analyses. These findings indicate that there exist significant clinical variability and mutational heterogeneities in Japanese patients with this syndrome.